TIDMGEN
-- TIVDAK is a First-in-Class Antibody-Drug Conjugate Directed to Tissue
Factor, a Protein Expressed on Cervical Cancer Cells
-- New Monotherapy Approved for Use in a Cancer with Limited Treatment
Options
COPENHAGEN, Denmark, and BOTHELL, Wash.; September 20, 2021 --
Genmab A/S
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(Nasdaq: GMAB) and Seagen
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Inc.
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(Nasdaq: SGEN) today announced that the U.S. Food and Drug
Administration (FDA) has granted accelerated approval to TIVDAK(TM)
(tisotumab vedotin-tftv), the first and only approved antibody-drug
conjugate (ADC) for the treatment of adult patients with recurrent
or metastatic cervical cancer with disease progression on or after
chemotherapy. TIVDAK is approved under the FDA's Accelerated
Approval Program based on tumor response and the durability of the
response. Continued approval may be contingent upon verification
and description of clinical benefit in confirmatory trials.(1)
"Once recurrent or metastatic cervical cancer progresses, there
is a need for more options for these patients," said Robert L.
Coleman, M.D., Chief Scientific Officer, US Oncology Research and
lead investigator of the innovaTV 204 clinical trial. "This is an
important development for patients with recurrent or metastatic
cervical cancer."
In the innovaTV 204 clinical trial, TIVDAK was evaluated in 101
patients with recurrent or metastatic cervical cancer who had
received no more than two prior systemic regimens in the recurrent
or metastatic setting, including at least one prior platinum-based
chemotherapy regimen. Results from the trial showed a 24 percent
confirmed objective response rate (ORR) (95% CI; 15.9-33.3), as
assessed by an independent review committee (IRC) using Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The
median duration of response (DOR) was 8.3 months (95% CI; 4.2 to
not reached).
The prescribing information for TIVDAK includes a BOXED WARNING
for ocular toxicity, and Warnings for peripheral neuropathy,
hemorrhage, pneumonitis, and embryo-fetal toxicity. The most common
(>=25%) adverse reactions, including laboratory abnormalities,
were hemoglobin decreased (52%), fatigue (50%), lymphocytes
decreased (42%), nausea (41%), peripheral neuropathy (39%),
alopecia (39%), epistaxis (39%), conjunctival adverse reactions
(37%), hemorrhage (32%), leukocytes decreased (30%), creatinine
increased (29%), dry eye (29%), prothrombin international
normalized ratio increased (26%), activated partial thromboplastin
time prolonged (26%), diarrhea (25%), and rash (25%). Please see
Important Safety Information below.(1)
"We are thrilled to see this new treatment approved by the FDA.
We are grateful to have another option for this devastating
disease," said Tamika Felder, Founder, Cervivor.
"TIVDAK's approval as a monotherapy in the U.S. is an important
milestone for women with recurrent or metastatic cervical cancer
with disease progression on or after chemotherapy, as they are in
need of a new treatment option and we look forward to making it
available to them, " said Jan van de Winkel, Ph.D., Chief Executive
Officer, Genmab. "The journey towards the approval of TIVDAK
started nearly two decades ago with innovative research by
scientists at Genmab and Seagen and reflects on our purpose of
making an impact in the lives of cancer patients and their
families. Today's announcement marks Genmab's evolution into a
fully integrated biotechnology company and we would like to thank
patients, caregivers, investigators and our collaborators for their
participation in our clinical studies."
"We are pleased with the accelerated approval of TIVDAK,
Seagen's third FDA-approved antibody-drug conjugate, and fourth
approved medicine. Our mission at Seagen is to develop medicines
that make a difference for people impacted by cancer," said Roger
Dansey, M.D., Chief Medical Officer, Seagen.
The Biologics License Application (BLA) for TIVDAK was submitted
in February 2021 and accepted with Priority Review in April 2021.
The submission was based on the results of the innovaTV 204
trial.
The FDA's Accelerated Approval Program allows for approval of a
medicine based on a surrogate endpoint that is reasonably likely to
predict clinical benefit, if the medicine fills an unmet medical
need for a serious condition. A global, randomized phase 3 clinical
trial (innovaTV 301) is underway and is also intended to support
global registrations.
About Cervical Cancer
It is estimated that in 2021, more than 14,480 new cases of
invasive cervical cancer will be diagnosed in the U.S., and 4,290
women will die from the disease.(2) Cervical cancer remains one of
the leading causes of cancer death in women globally, with over
311,000 women dying of the disease in 2018.(3)
About the innovaTV 204 Trial
The innovaTV 204 trial (NCT03438396/GOG-3023/ENGOT-cx6) is an
open-label, multicenter, single-arm Phase 2 trial that evaluated
tisotumab vedotin in 101 patients with recurrent or metastatic
cervical cancer who had received no more than two prior systemic
regimens in the recurrent or metastatic setting, including at least
one prior platinum-based chemotherapy regimen. Patients were
excluded if they had active ocular surface disease, any prior
episode of cicatricial conjunctivitis or Stevens-Johnson syndrome,
Grade >=2 peripheral neuropathy or known coagulation defects
leading to an increased risk of bleeding. The main efficacy outcome
measures were confirmed ORR per RECIST v1.1 as assessed by an IRC
and DOR.(1)
The study was conducted by Genmab in collaboration with Seagen,
European Network of Gynaecological Oncological Trial Groups (ENGOT)
and the GOG Foundation, Inc. (GOG). For more information about the
phase 2 innovaTV 204
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clinical trial and other clinical trials with tisotumab vedotin,
please visit www.clinicaltrials.gov.
About TIVDAK (tisotumab vedotin-tftv)
TIVDAK (tisotumab vedotin-tftv) is an ADC composed of Genmab's
human monoclonal antibody directed to tissue factor (TF) and
Seagen's ADC technology that utilizes a protease-cleavable linker
that covalently attaches the microtubule-disrupting agent
monomethyl auristatin E (MMAE) to the antibody. Nonclinical data
suggests that the anticancer activity of TIVDAK is due to the
binding of the ADC to TF expressing cancer cells, followed by
internalization of the ADC-TF complex, and release of MMAE via
proteolytic cleavage. MMAE disrupts the microtubule network of
actively dividing cells, leading to cell cycle arrest and apoptotic
cell death. In vitro, TIVDAK also mediates antibody-dependent
cellular phagocytosis and antibody-dependent cellular
cytotoxicity.(1)
TIVDAK (tisotumab vedotin-tftv) for injection, for intravenous
use, 40 mg Important Safety Information
BOXED WARNING: OCULAR TOXICITY
TIVDAK caused changes in the corneal epithelium and conjunctiva
resulting in changes in vision, including severe vision loss, and
corneal ulceration. Conduct an ophthalmic exam at baseline, prior
to each dose, and as clinically indicated. Adhere to premedication
and required eye care before, during and after infusion. Withhold
TIVDAK until improvement and resume, reduce the dose, or
permanently discontinue, based on severity.
Warnings and Precautions
Ocular Adverse Reactions occurred in 60% of patients with
cervical cancer treated with TIVDAK. The most common were
conjunctival adverse reactions (40%), dry eye (29%), corneal
adverse reactions (21%), and blepharitis (8%). Grade 3 ocular
adverse reactions occurred in 3.8% of patients, including severe
ulcerative keratitis in 3.2% of patients. One patient experienced
ulcerative keratitis with perforation requiring corneal
transplantation. Cases of symblepharon were reported in patients
with other tumor types treated with TIVDAK at the recommended
dose.
In innovaTV 204, 4% of patients experienced visual acuity
changes to 20/50 or worse, including 1% of patients who experienced
a visual acuity change to 20/200. Of the patients who experienced
decreased visual acuity to 20/50 or worse, 75% resolved, including
the patient who experienced decreased visual acuity to 20/200.
Refer patients to an eye care provider for an ophthalmic exam
including visual acuity and slit lamp exam at baseline, prior to
each dose, and as clinically indicated. Adhere to premedication and
required eye care to reduce the risk of ocular adverse reactions.
Promptly refer patients to an eye care provider for any new or
worsening ocular signs and symptoms. Withhold dose, reduce the
dose, or permanently discontinue TIVDAK based on the severity of
the adverse reaction.
Peripheral neuropathy (PN) occurred in 42% of cervical cancer
patients treated with TIVDAK across clinical trials; 8% of patients
experienced Grade 3 PN. PN adverse reactions included peripheral
neuropathy (20%), peripheral sensory neuropathy (11%), peripheral
sensorimotor neuropathy (5%), motor neuropathy (3%), muscular
weakness (3%), and demyelinating peripheral polyneuropathy (1%).
One patient with another tumor type treated with TIVDAK at the
recommended dose developed Guillain- Barré syndrome.
Monitor patients for signs and symptoms of neuropathy. For new
or worsening PN, withhold, dose reduce, or permanently discontinue
TIVDAK based on the severity of PN.
Hemorrhage occurred in 62% of cervical cancer patients treated
with TIVDAK across clinical trials. The most common all grade
hemorrhage adverse reactions were epistaxis (44%), hematuria (10%),
and vaginal
hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients.
Monitor patients for signs and symptoms of hemorrhage. For
patients experiencing pulmonary or CNS hemorrhage, permanently
discontinue TIVDAK. For Grade >=2 hemorrhage in any other
location, withhold until bleeding has resolved, blood hemoglobin is
stable, there is no bleeding diathesis that could increase the risk
of continuing therapy, and there is no anatomical or pathologic
condition that can increase the risk of hemorrhage recurrence.
After resolution, either resume treatment or permanently
discontinue TIVDAK.
Pneumonitis: Severe, life-threatening, or fatal pneumonitis can
occur in patients treated with antibody-drug conjugates containing
vedotin, including TIVDAK. Among patients with cervical cancer
treated with TIVDAK across clinical trials, 2 patients (1.3%)
experienced pneumonitis, including 1 patient who had a fatal
outcome.
Monitor patients for pulmonary symptoms indicative of
pneumonitis. Infectious, neoplastic, and other causes for symptoms
should be excluded through appropriate investigations.
Withhold TIVDAK for patients who develop persistent or recurrent
Grade 2 pneumonitis and consider dose reduction. Permanently
discontinue TIVDAK in all patients with Grade 3 or 4
pneumonitis.
Embryo-fetal toxicity: TIVDAK can cause fetal harm when
administered to a pregnant woman. Advise patients of the potential
risk to a fetus. Advise females of reproductive potential to use
effective contraception during treatment with TIVDAK and for 2
months after the last dose. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with TIVDAK and for 4 months after the last
dose.
Adverse Reactions
Serious adverse reactions occurred in 43% of patients; the most
common (>=3%) were ileus (6%), hemorrhage (5%) pneumonia (4%),
PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse
reactions occurred in 4% of patients who received TIVDAK, including
septic shock, pneumonitis, sudden death, and multisystem organ
failure (each 1%).
Adverse reactions leading to permanent discontinuation occurred
in 13%
of patients receiving TIVDAK; the most common (>=3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (>=3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (>=3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).
The most common (>=25%) adverse reactions, including
laboratory abnormalities, were hemoglobin decreased (52%), fatigue
(50%), lymphocytes decreased (42%), nausea (41%), PN (39%),
alopecia (39%), epistaxis (39%), conjunctival adverse reactions
(37%), hemorrhage (32%), leukocytes decreased (30%), creatinine
increased (29%), dry eye (29%), prothrombin international
normalized ratio increased (26%), activated partial thromboplastin
time prolonged (26%), diarrhea (25%), and rash (25%).
Drug interactions
Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4
inhibitors may increase unconjugated monomethyl auristatin E (MMAE)
exposure, which may increase the risk of TIVDAK adverse reactions.
Closely monitor patients for TIVDAK adverse reactions.
Use in Specific Populations
Moderate or Severe Hepatic Impairment: MMAE exposure and adverse
reactions are increased. Avoid use.
Lactation: Advise lactating women not to breastfeed during
TIVDAK treatment and for at least 3 weeks after the last dose.
Please see full prescribing information, including BOXED WARNING
for TIVDAK
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here.
About Genmab
Genmab is an international biotechnology company with a core
purpose to improve the lives of people with cancer. For more than
20 years, Genmab's vision to transform cancer treatment has driven
its passionate, innovative and collaborative teams to invent
next-generation antibody technology platforms and leverage
translational research and data sciences, fueling multiple
differentiated cancer treatments that make an impact on people's
lives. To develop and deliver novel therapies to patients, Genmab
has formed 20+ strategic partnerships with biotechnology and
pharmaceutical companies. Genmab's proprietary pipeline includes
bispecific T-cell engagers, next-generation immune checkpoint
modulators, effector function enhanced antibodies and antibody-drug
conjugates.
Genmab is headquartered in Copenhagen, Denmark with locations in
Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo,
Japan. For more information, please visit Genmab.com
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and follow us on Twitter.com/Genmab
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.
About Seagen
Seagen is a global biotechnology company that discovers,
develops and commercializes transformative cancer medicines to make
a meaningful difference in people's lives. Seagen is headquartered
in the Seattle, Washington area, and has locations in California,
Canada, Switzerland and the European Union. For more information on
our marketed products and robust pipeline, visit www.seagen.com and
follow @SeagenGlobal
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on Twitter.
About the Seagen and Genmab Collaboration
Tisotumab vedotin is being co-developed by Genmab and Seagen,
under an agreement in which the companies share costs and profits
for the product on a 50:50 basis.
Genmab A/S Contacts:
For Media:
Marisol Peron, Senior Vice President, Global Investor Relations
& Communications
T: +1 609 524 0065; E: mmp@genmab.com
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For Investor Relations:
Andrew Carlsen, Vice President, Head of Investor Relations
T: +45 3377 9558; E: acn@genmab.com
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Seagen Contacts:
For Media:
David Caouette
Vice President, Corporate Communications
(310) 430-3476
dcaouette@seagen.com
For Investor Relations:
Peggy Pinkston
Senior Vice President, Investor Relations
(425) 527-4160
ppinkston@seagen.com
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Genmab Forward Looking Statements
This Company Announcement contains forward looking statements.
The words "believe", "expect", "anticipate", "intend" and "plan"
and similar expressions identify forward looking statements. Actual
results or performance may differ materially from any future
results or performance expressed or implied by such statements. The
important factors that could cause our actual results or
performance to differ materially include, among others, risks
associated with pre-clinical and clinical development of products,
uncertainties related to the outcome and conduct of clinical trials
including unforeseen safety issues, uncertainties related to
product manufacturing, the lack of market acceptance of our
products, our inability to manage growth, the competitive
environment in relation to our business area and markets, our
inability to attract and retain suitably qualified personnel, the
unenforceability or lack of protection of our patents and
proprietary rights, our relationships with affiliated entities,
changes and developments in technology which may render our
products or technologies obsolete, and other factors. For a further
discussion of these risks, please refer to the risk management
sections in Genmab's most recent financial reports, which are
available on www.genmab.com and the risk factors included in
Genmab's most recent Annual Report on Form 20-F and other filings
with the U.S. Securities and Exchange Commission (SEC), which are
available at www.sec.gov. Genmab does not undertake any obligation
to update or revise forward looking statements in this Company
Announcement nor to confirm such statements to reflect subsequent
events or circumstances after the date made or in relation to
actual results, unless required by law.
Genmab A/S and/or its subsidiaries own the following trademarks:
Genmab(R); the Y-shaped Genmab logo(R); Genmab in combination with
the Y-shaped Genmab logo. TIVDAK(TM) and the TIVDAK logo are
trademarks owned by Seagen Inc.
Seagen Forward Looking Statements
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the continued FDA
approval of TIVDAK (tisotumab vedotin-tftv) for the treatment of
adult patients with recurrent or metastatic cervical cancer with
disease progression on or after chemotherapy; the conduct of an
ongoing randomized phase 3 clinical trial (innovaTV 301) intended
to verify the clinical benefit of TIVDAK and support global
registrations; and the therapeutic potential of TIVDAK, including
its efficacy, safety and therapeutic uses. Actual results or
developments may differ materially from those projected or implied
in these forward-looking statements. Factors that may cause such a
difference include the possibility that innovaTV 301 and subsequent
clinical trials may fail to establish sufficient efficacy; that
adverse events or safety signals may occur; that utilization and
adoption of TIVDAK by prescribing physicians may be limited by the
availability and extent of reimbursement and other factors; and
that adverse regulatory actions may occur. More information about
the risks and uncertainties faced by Seagen is contained under the
caption "Risk Factors" included in the Company's Quarterly Report
on Form 10-Q for the quarter ended June 30, 2021 filed with the
Securities and Exchange Commission. Seagen disclaims any intention
or obligation to update or revise any forward-looking statements,
whether as a result of new information, future events or otherwise,
except as required by law.
References
(1) (TIVDAK) ([package insert]. Bothell, WA:) (Seagen) (,
Inc.)
(2 Cancer Stat Facts: Cervical Cancer. National Cancer Institute
website.)
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(https://seer.cancer.gov/statfacts/html/cervix.html) (. Accessed)
(September 16) (, 2021) (.)
(3 Bray F,) (Ferlay) (J,) (Soerjomataram) (I, et al. Global
Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and
Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J
Clin 2018;0: 1-31.)
# # #
Attachment
-- 200921_CA62_innovaTV 204 Approval
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(END) Dow Jones Newswires
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